Our initial characterization of Dengue-infection-related immune repertoire has been ofthe B cell repertoires following different modes of infection-based pathology. This work combines a collaborative component (cells and patient information from Eva Harris, Poornima Parameswaran, and their colleagues), experimental manipulations to amplify receptor populations, and computational analysis of amplified sequences from high throughput immunome analysis. The past four months has provided our first detailed look at receptor repertoires in Dengue infection, and to my knowledge the first such analysis anywhere, yielding a number of rather striking observations that suggest both biological hypotheses and experimental followup. Although preliminary, these give a strong indication ofthe value of applying immunome analysis to infectious systems, (i) We observe, as with the original small scale sequencing set carried out in 2010, a strong clonal response in a subset of individuals with pathogenic conditions related to Dengue. (ii)We observe a reproducible appearance of small clones of cells who's appearance coincides with an infectious event but which persist for at least six months after exposure, (iii) We observe different patterns of appearance and maturation in Dengue 2 and Dengue 3 cohorts, suggesting potential mechanisms for the serotype-specific properties of these infectious agents in their effects (short and long-term) on the host. Followup work in this area will provide us the opportunity to determine the generality and significance of these observations and to addresses a series of specific questions related to understanding and management of infection: (i) Will receptor profiling be a valuable adjunct in identifying Dengue-related syndromes and predicting cases that will be severe? (ii) Will receptor profiles of Dengue cases provide specific candidates for immune receptor molecules that mediate unhealthy immune effects during secondary infection? (iii) Will the molecular signatures obtained from this analysis (combined with the extensive analysis in a number of other groups of additional molecular and immunological markers) be a useful clinical tool in guiding

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI065359-09
Application #
8462565
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
9
Fiscal Year
2013
Total Cost
$134,248
Indirect Cost
$13,343
Name
University of California Irvine
Department
Type
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Hertz, Tomer; Beatty, P Robert; MacMillen, Zachary et al. (2017) Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections. J Immunol 198:4025-4035
Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299
Parameswaran, Poornima; Wang, Chunling; Trivedi, Surbhi Bharat et al. (2017) Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections. Cell Host Microbe 22:400-410.e5
Bortell, Nikki; Flynn, Claudia; Conti, Bruno et al. (2017) Osteopontin Impacts West Nile virus Pathogenesis and Resistance by Regulating Inflammasome Components and Cell Death in the Central Nervous System at Early Time Points. Mediators Inflamm 2017:7582437
Barbour, Alan G (2017) Infection resistance and tolerance in Peromyscus spp., natural reservoirs of microbes that are virulent for humans. Semin Cell Dev Biol 61:115-122
Nualnoi, Teerapat; Norris, Michael H; Tuanyok, Apichai et al. (2017) Development of Immunoassays for Burkholderia pseudomallei Typical and Atypical Lipopolysaccharide Strain Typing. Am J Trop Med Hyg 96:358-367
Nakajima, Rie; Escudero, Raquel; Molina, Douglas M et al. (2016) Towards Development of Improved Serodiagnostics for Tularemia by Use of Francisella tularensis Proteome Microarrays. J Clin Microbiol 54:1755-65
Zeltina, Antra; Bowden, Thomas A; Lee, Benhur (2016) Emerging Paramyxoviruses: Receptor Tropism and Zoonotic Potential. PLoS Pathog 12:e1005390
Ziegler, Christopher M; Eisenhauer, Philip; Bruce, Emily A et al. (2016) A novel phosphoserine motif in the LCMV matrix protein Z regulates the release of infectious virus and defective interfering particles. J Gen Virol 97:2084-9
Park, Arnold; Yun, Tatyana; Hill, Terence E et al. (2016) Optimized P2A for reporter gene insertion into Nipah virus results in efficient ribosomal skipping and wild-type lethality. J Gen Virol 97:839-43

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